The aim of this project is to construct and characterize a new type of hybrid retrovirus that will use a novel replication strategy. This replication strategy will make the virus safer for use, either as a therapeutic or a preventive tool. It is the specific aim of this project to engineer this virus to allow for replication in human cells. The general objective of the project is to adapt this hybrid virus for use in gene therapy and for vaccines. Because of the obvious importance of safety issues to public health and medicine, these new retroviral entities will have broad application in biotechnology and medicine as safer, and perhaps more efficient, vectors for transfer of genes into animals and humans in need of gene therapy and as safer vaccines against viral disease and cancer. The hybrid viruses will be constructed and tested using standard molecular biology techniques, and they will consist entirely of available DNA plasmid sequences. These novel retroviruses will open a new field into research of retroviral replication that will result in a better understanding of this process and could potentially lead to a new and more efficient approaches in treatment of viral diseases. PROPOSED COMMERCIAL APPLICATION: The potential commercial applications of this research are: in health care and medicine, more specifically in gene therapy, anti-viral vaccines, and cancer vaccines.